Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia
Abstract The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This st...
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2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86390-4 |
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| author | Mian Li Yue Wu Yan Xu Xin Huang Kerun Gao Nannan Hu Shuangyue Zhu Chengpeng Wang Sugai Liang |
| author_facet | Mian Li Yue Wu Yan Xu Xin Huang Kerun Gao Nannan Hu Shuangyue Zhu Chengpeng Wang Sugai Liang |
| author_sort | Mian Li |
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| description | Abstract The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This study included 38 drug-naive patients with FES and 43 healthy controls (HCs). Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Levels of TRP-KYN metabolites in serum and urine were quantified. Patients with FES showed significantly higher serum quinolinic acid/kynurenic acid (QUIN/KYNA) ratio and urine KYN/TRP ratio compared to HCs, while neuroprotective metabolites, including serum KYNA, xanthurenic acid (XA), and urine picolinic acid (PIC) levels, were significantly reduced, along with a decreased urine PIC/QUIN ratio (p < 0.05). The urine KYNA/KYN ratio was negatively correlated with PANSS general psychopathology scores (r = -0.35, p = 0.04) and with PANSS total scores (r = -0.35, p = 0.046). Patients with FES exhibited dysregulation of the peripheral TRP-KYN pathway, characterized by an increased neurotoxic-to-neuroprotective QUIN/KYNA ratio and reduced levels of neuroprotective metabolites. This shift towards increased neurotoxic product generation suggests that the dysregulation of the TRP-KYN pathway could play a role in the pathophysiology of schizophrenia. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-e41581babb554a72a138dc9b3203f5bf2025-01-19T12:23:43ZengNature PortfolioScientific Reports2045-23222025-01-011511810.1038/s41598-025-86390-4Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophreniaMian Li0Yue Wu1Yan Xu2Xin Huang3Kerun Gao4Nannan Hu5Shuangyue Zhu6Chengpeng Wang7Sugai Liang8Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAffiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of MedicineAbstract The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This study included 38 drug-naive patients with FES and 43 healthy controls (HCs). Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Levels of TRP-KYN metabolites in serum and urine were quantified. Patients with FES showed significantly higher serum quinolinic acid/kynurenic acid (QUIN/KYNA) ratio and urine KYN/TRP ratio compared to HCs, while neuroprotective metabolites, including serum KYNA, xanthurenic acid (XA), and urine picolinic acid (PIC) levels, were significantly reduced, along with a decreased urine PIC/QUIN ratio (p < 0.05). The urine KYNA/KYN ratio was negatively correlated with PANSS general psychopathology scores (r = -0.35, p = 0.04) and with PANSS total scores (r = -0.35, p = 0.046). Patients with FES exhibited dysregulation of the peripheral TRP-KYN pathway, characterized by an increased neurotoxic-to-neuroprotective QUIN/KYNA ratio and reduced levels of neuroprotective metabolites. This shift towards increased neurotoxic product generation suggests that the dysregulation of the TRP-KYN pathway could play a role in the pathophysiology of schizophrenia.https://doi.org/10.1038/s41598-025-86390-4SchizophreniaTryptophan-kynurenine pathwayPeripheral metabolitesNeurotoxicityNeuroprotection |
| spellingShingle | Mian Li Yue Wu Yan Xu Xin Huang Kerun Gao Nannan Hu Shuangyue Zhu Chengpeng Wang Sugai Liang Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia Scientific Reports Schizophrenia Tryptophan-kynurenine pathway Peripheral metabolites Neurotoxicity Neuroprotection |
| title | Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia |
| title_full | Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia |
| title_fullStr | Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia |
| title_full_unstemmed | Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia |
| title_short | Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia |
| title_sort | peripheral tryptophan kynurenine pathway dysfunction in first episode schizophrenia |
| topic | Schizophrenia Tryptophan-kynurenine pathway Peripheral metabolites Neurotoxicity Neuroprotection |
| url | https://doi.org/10.1038/s41598-025-86390-4 |
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